Unilateral vocal-fold paralysis is a major complication from thyroid surgery and commonly results from trauma to the recurrent laryngeal nerve (RLN). The loss of tone in the intrinsic muscles of the larynx due to RLN injury can eliminate voice, produce breathing difficulties, and significantly increase risk for aspiration. For crush injuries o the RLN, the only treatment is watchful waiting for spontaneous regeneration of axons and reinnervation of laryngeal muscles. For transected RLNs, the preferred treatment is surgical anastomosis of nerve segments followed by the same hopes for spontaneous regeneration and reinnervation. Both treatments can restore muscle tone, but reinnervation is inefficient and takes many months. Even then, purposeful movement of the vocal folds and complete glottic closure are not restored because of synkinesis from aberrant reinnervation, but, as long as there is reinnervation, laryngeal function can be further improved with surgical manipulation of laryngeal muscles. In this project, we will develop tools for producing controlled injury and test the efficacy of a simple, safe pharmacological treatment to significantly accelerate reinnervation. In Aim 1, we will develop quantitatively reproducible RLN crush injuries and quantitative techniques for the study of resulting vocal fold paralysis and functional reinnervation. In Aim 2, we will test the hypothesis that continuous lithium administration accelerates reinnervation after RLN crush injury. Lithium modulates glycogen synthase kinase 3 in the neurotrophin pathway and promotes growth-cone activity and neurite extension. For both aims, functional outcomes will be monitored at regular intervals by vocalization analysis, plethysmography, quantitative video laryngoscopy, and larynx electromyography. The results of this multidisciplinary collaboration between physicians and basic scientists will have direct practical clinical impact on the treatment of patients with unilateral vocal-fold paralysis. The quantitative tools for nerve injury and functional assessment, and the pharmacological treatment to accelerate axonal sprouting and reinnervation will have significant impact on all types of peripheral nerve injury.